Graves disease isthemostcommonformofhyperthyroidism. Itoccursmostfrequentlybetweentheagesof20and50andis10timesmorecommoninwomenthaninmen.GravesdiseaseisanautoimmunedisorderinwhichactivatingautoantibodiesareproducedagainsttheTSHreceptor.Hyperthyroidismdrivenbytheantibodyisoftenaccompaniedbyadiffusegoiterasaresultofhyperplasiaandhypertrophyofthegland.Thefollicularepithelialcellsbecometallcolumnarcells,andthecolloidshowsascallopedperipheryindicativeofrapidturnover.
TheprimaryclinicalstatefoundinGravesdiseaseisthyrotoxicosis—thestateofexcessivethyroidhormoneinbloodandtissues.Apatientwiththyrotoxicosispresentsoneofthemoststrikingpicturesinclinicalmedicine.Thelargeincreaseinmetabolicrateismanifestedasweightlossdespiteincreasedfoodintake.Excessheatproductioncausesdiscomfortinwarmenvironments,sweating,andgreaterintakeofwater.Theincreaseinadrenergicactivityproducesarapidheartrate,hyperkinesis,tremor,nervousness,andawide-eyedstare.Weaknessiscausedbyalossofmusclemassaswellasimpairedmusclefunction.Othersymptomsincludealabileemotionalstate,breathlessnessduringexercise,anddifficultyswallowingorbreathingbecauseofcompressionoftheesophagusortracheabytheenlargedthyroidgland.Themostcommoncardiovascularsignissinustachycardia.There
Perhaps the most clinically important actions of thyroid hormone are those on cardiovascular physiology. T3 increases cardiac output, thereby ensuring sufficient O2 delivery to tissues (
Fig. 42.11). The resting heart rate and stroke volume are increased. The speed and force of myocardial contractions are enhanced (positive chronotropic and inotropic effects, respectively), and the diastolic relaxation isincreasedcardiacoutputassociatedwithawidenedpulsepressuresecondarytoapositiveinotropiceffectcoupledwithdecreasedsystemicvascularresistance.AmajorclinicalsigninGravesdiseaseisexophthalmos (abnormalprotrusionoftheeyeball)andperiorbital edema. ThisiscausedbyautoantibodybindingtotheTSHreceptorexpressedonorbitalfibrocytes,leadingtoproductionofinflammatorycytokines.
GravesdiseaseisusuallydiagnosedbyelevatedserumfreeandtotalT4andT3andtheclinicalsignsofdiffusegoiterandophthalmopathy.SerumTSHlevelsarelowbecausethehypothalamusandpituitaryareinhibitedbythehighlevelsofT4andT3.Inmostcases,radioiodineuptakebythethyroidisexcessiveanddiffuse.AssayofTSHlevelsandthepresenceofcirculatingthyroidstimulatingimmunoglobulinwilldistinguishGravesdisease(aprimarydisorder)fromarareadenomaofpituitarythyrotrophs(asecondarydisorder)thatproduceshighlevelsofTSH.
TreatmentofGravesdiseaseisusuallyremovalofthethyroidtissue,followedbylifelongreplacementtherapywithT4.Thyroidtissuecanberemovedeitherbyradioablationwith131Iorbysurgery.Withsurgicalremovalofthegland,precautionsmustbetakentoavoidamassive,potentiallylife-threateningreleaseofthyroidhormonesknownasthyroid storm. Analternativetoremovalofthyroidtissueisadministrationofantithyroid drugs thatinhibitTPOactivity.